Assembling his 'Tamoxifen Team'

BY
MD Anderson staff

It’s the Friday before Father’s Day, and V. Craig Jordan, Ph.D., who’s considered the “Father of Tamoxifen,” is sitting down to talk about, among other things, the drug for which he’s best known, the class of drugs he plans to build in his lab at MD Anderson Cancer Center and his decision to come to Texas.

Born in New Braunfels, Texas, and raised in England, Jordan has dual British and U.S. citizenship. In 2002, he received the Order of the British Empire from Queen Elizabeth II for services to international breast cancer research. In his free time, he has amassed an impressive collection of antique weapons, including a Viking sword made in England around A.D. 860.

On what he’s famous for …

The National Academy of Sciences member played a key role in transforming a once-failed contraceptive medication into a valuable breast cancer treatment responsible for saving countless lives. The drug, later named tamoxifen, originally was created to block estrogen in the hopes of preventing pregnancy. Jordan discovered the drug could be used to block the estrogen that fuels estrogen receptor (ER)-positive breast cancer cells, and developed the strategy of using tamoxifen as a long-term adjuvant therapy. It’s used to treat all stages of breast cancer, ductal carcinoma in situ and male breast cancer.

He also described and deciphered the properties of a new group of medicines, which includes tamoxifen, called selective estrogen receptor modulators (SERMs). He was the first to discover the preventive abilities not only of tamoxifen but also of raloxifene. The Food and Drug Administration (FDA) has approved both drugs for reducing breast cancer incidence in high-risk women.

“Today, there are five SERMs that are FDA approved. In 1980, there were none. It’s changed medicine completely.”

The professor of Breast Medical Oncology and Molecular and Cellular Oncology’s focus at MD Anderson is the new biology of estrogen-induced cell death. He and his “Tamoxifen Team” will work to develop translational approaches for treating and preventing cancer.

Give us an update on the startup of your lab.

I’m currently gathering my “Tamoxifen Team.” It’s converging this summer. There are a lot of variables — people getting their degrees, work permits, visas. We should have a critical mass of 10 people in place by August or September.

What will the initial focus of your work be once the lab is up and running?

How does endocrine or hormone therapy fail? The reason I came to MD Anderson is the opportunity to do translational research. We have all the best models from cell culture lines that you can get anywhere. But the reality now is we need it connected to patients. We want to create cell cultures that represent the spectrum of breast cancer. We want to make 50 breast cancer cell lines and link those to patient information. We then sequence all of this and the result is we have everyone’s cell lines.

We want to put together a battery of model systems in the lab that will allow the next generation of researchers to study cell lines that link to patients’ diseases. But then ask the question, “with this estrogen-induced apoptosis, how is it that these ER-positive breast cancers have in their genes the ability to unmask dying with the thing that should keep them alive?” This is a problem we’re going to tackle by studying bone remodeling. When estrogen is cut off in menopausal women, bone loss occurs. Macrophages, which destroy foreign antigens, go into the bone, which is beginning to decay, and start to clean it up. Those macrophages basically become a cell called an osteoclast, which destroys bone. But what happens when estrogen comes back into the bone? It kills the osteoclast.

If we can look at the mechanism of how this happens, and we follow the estrogen receptor to where the target is in women’s breasts, that target becomes a “druggable” target for, maybe, any cancer. It could be a perfect symbiosis with what James Allison is doing with immunotherapy — using the body’s systems to protect itself. That’s where we want to go.

What appealed to you about MD Anderson?

To me, science and, specifically, medical science, is all about creating change that will benefit society. It’s a privilege to be given the chance to provide something for society, and change society. And that change has to be on the cutting edge. With the offer to come to MD Anderson, I knew I would be in a great position to continue to bring about change.

Speaking of change, what changes do you see in the future that can be addressed today at MD Anderson?

As the population continues to get older, there will be a 50% increase in breast cancer. This will be almost exclusively estrogen-receptor positive. What we do now will position MD Anderson to be a leader in estrogen receptor-positive therapeutics for the majority of breast cancer. So it’s a strategic decision to get a handle on the disease now in order to cope with the increase the next generation of physicians will be facing. Currently, 80% of breast cancers are ER-positive, but that percentage is expected to increase to 95% as the population ages.

And you’re familiar with Texas, right?

I was born in Texas, so coming back to Texas is like coming back to my natural home. As it turns out, my mother’s best friend, who she hasn’t seen for decades, lives two miles down the road from me. Whatever is in my native DNA — my father was from Dallas — seems to have brought me back here.

Now that you’ve been here a few months, what are your initial impressions of the institution?

We have a great opportunity here. The whole world is struggling with how we forge a future. We have limited resources, but I’m very impressed with what the state of Texas is doing through CPRIT. It’s a model that works. By funding cancer research, we can attract the brightest minds in the field to Houston. The resources at MD Anderson are second to none, and those resources are deployed optimally to give optimal health care, hire optimal faculty and conduct optimal research. There’s a vision of research here that says, “here’s what we need to do: end cancer. Now, let’s try and do it. Take what resources we have and answer real questions. Take everyone we have and bring them together to do it. Recruit people who can think outside the box.” The fact that the state has made a commitment to supporting that goal, and the fact that Chancellor (William) McRaven has a great vision for the future — all of this is why I want to be here. I can’t say there’s any place else that has this constellation of stars all lining up.